ISDN2012_0270: Development of respiratory rhythm generating circuits in the mouse embryo hindbrain

Neurobiologie & Developpement, CNRS UPR3294, Inst. de Neurobiol. Alfred Fessard, Gif-sur-Yvette, France We breathe roughly half a billion times in a lifetime, generally in an effortless and even unconscious manner owing to activity of a respiratory central pattern generator (CPG) located in the hindbrain. The respiratory CPG relies on the coupling of two prominent rhythmogenic sites located in the medulla, the pre-Bötzinger Complex (preBötC) and the para-Facial Respiratory Group (pFRG). Working in the mouse embryo, we have identified the emergence of forerunning versions of these two oscillators using developmental genetics tools, electrophysiological and optical recordings. We have defined molecular and functional signatures for cells composing each oscillator. More precisely, data will be presented showing the independent developments of (i) an Egr2(also known as Krox20) derived, Phox2b/Lbx1/Atoh1-expressing embryonic parafacial oscillator and (ii) a Dbx1-derived populations of glutamatergic interneurons required for both preBötC rhythm generation and bilateral synchrony through Robo3-dependent axonal commissural pathfinding. These results indicate that each oscillator is not assembled from cells of disparate origins. Rather, each oscillator is made of cells with selective built-in functional properties that derive from a discrete transcriptionally defined domain of the neuroepithelium. Hence, the dual organisation of the respiratory CPG seems to reflect the modular origin of its composing cells. Work supported by CNRS, INSERM, ANR grants to GF.